Can glaucoma be cured?

Take Home Points

There is presently no cure

Successful treatment can stop meaningful vision loss

Nerve cell replacement research has taken initial steps

When she was 90 years old, my wonderful Grandma Mamie told me she
was having trouble putting on pullover sweaters because her shoulders had
arthritis. “Harry,” she asked, “you’re at that medical school Johns
Hopkins, when is my shoulder going to get better?” I had to help her
understand that we weren’t going to cure her shoulder, but we could buy
her button-up sweaters. An important part of helping persons with glaucoma
is to channel that hopefulness that Mamie expressed into flexibility to
deal with what they’ve got. (Mamie kept winning at Bingo and playing
bridge for some time afterward).

In this section, we’ll discuss two forms of definitive treatment for
glaucoma, one may happen in the future, and one is what we can do now. The
future hope is to restore vision that has been lost. That can’t presently
be done. The present treatments can slow the process so much that no
meaningful loss occurs in the person’s lifetime. Successful glaucoma
surgery can lower eye pressure to a safe level(see Operations for glaucoma)see section Operations for glaucoma.
Such surgery can last for many years without need for any eye drops or
medicines. But, since there are some surgery eyes that start needing
medicine or more surgery again later, it is important to keep having
doctor’s exams regularly even when successful surgery has been done. So,
checkups will be needed, just as they are for other serious illnesses
where a remission has been produced, to be sure it doesn’t come back. For
now, we have several ways to lower eye pressure to really slow vision loss
from glaucoma.

As described already, the successful treatment for most persons with
glaucoma is to take daily eye drops indefinitely. Several laboratories and
companies are presently working on a variety of ways that the medicine for
glaucoma could be given only once or twice per year. These approaches will
probably include placing the medicine as a deposit under the surface of
the eye or even inside the eye in the doctor’s office under sterile
conditions. This may sound scary, but for another eye disease called
age-related macular degeneration, inside the eye injections every month
are already proving to be a sight restoring method that older persons find
easy to tolerate. This could really increase the number of those with
glaucoma who no longer need to take eye drops every day.

There are several things that could be placed on or in the eye that
could help. Some would be drugs in a long-lasting formula that lower eye
pressure. Others would be modified virus particles that
get inside the eye cells in the front or back of the eye. Once inside
these viral carriers fool the cells into thinking that the DNA they carry
should be translated like a normal gene and the substance that is produced
is made by the cell as if it were a natural molecule. The Glaucoma Center
of Excellence team has already tested several such molecules that slow
glaucoma damage in animal models of glaucoma. Ideally, one injection of
such a viral carrier would last for years to protect the eye. This may
sound like Star Wars, but one eye disease called Leber’s congenital
amaurosis has already been helped dramatically in human eyes by this type
of approach. People with that disease have the fortunate situation that
when the viral carrier was injected, they actually saw better. This
insertion of DNA is called gene therapy, and there are active research
programs to use this approach for glaucoma.

Gene therapy is only one of the things now being included in the
approach called neuroprotection research for glaucoma. This type of
treatment, when it becomes available, will involve any method that keeps
nerve cells alive longer—and preserves the vision that the person has at
that time. But, gene therapy and neuroprotection will not restore lost
vision. In general, these methods do not try to lower eye pressure, but
rather they make the eye or the nerve cells less likely to suffer from the
effects of eye pressure and the other negative things that glaucoma does.
We now have more than a dozen types of potential neuroprotective drugs
that have been shown to work in this way in mice, rats, and even monkeys.
One full trial of a drug called Memantine in over 1,000 patients was
conducted to see if the pill would slow the rate of peripheral visual loss
in glaucoma patients. The drug didn’t work well enough to be recommended
for patients with glaucoma, but some large drug companies are actively
researching this area. A very small study tested whether one of our
existing eye drops for glaucoma has additional benefit as a
neuroprotectant. Unfortunately, the data from this study were never made public. When we talk to glaucoma patients and their
families, there is often a wonderful hopefulness that adding some
treatment to the standard approaches will be helpful. Consideration of the
things that are called “alternative therapies” is given in section Are
there treatments other than lowering eye pressure?see section Are there treatments other than lowering eye pressure?

Standard glaucoma treatment has been shown to slow the progress of
the disease in the majority of patients to such an extent that they never
become more impaired than they are at the time they discover they have the
disease. That isn’t a cure, but it is a comfort. But, for those who have
very significant vision loss from glaucoma, the hope is that we will find
a way to restore vision. For some eye problems, there are actual
improvements to be expected from treatment. Cataract means that the lens
inside the eye has become clouded. Surgery is commonly done to remove the
foggy lens and replace it with an artificial one. Cataract surgery
routinely restores normal vision to those for whom cataract was the only
problem. Yet, in glaucoma, the loss of vision is due to death of the nerve
cells called ganglion cells. These cells do not replace themselves as our
skin cells do, for example.

So, to be able to restore vision, we must put back a lot of nerve
cells. And, they can’t just be thrown into the retina, they have to go in
the places where previous ones lived. And, they have to link up on one end
with the other retinal nerve cells they normally get information from, as
well as to grow a fiber along those 2 inches up to the brain, and link up
with the partner cells in the next relay station. And, the connections
(synapses) need to be made in a way that produces useful vision images,
without messing up the existing connections for the parts of vision that
haven’t been lost from glaucoma already.

As you can see, that’s a lot of “And”s. But, 10 years ago, I held a
meeting of scientists in which all the group talked about was how
impossible it would ever be to restore vision in glaucoma. My lab and
other research groups went to work and since then we’ve accomplished some
of the initial steps. First, we know where we can get the nerve cells that
we need. Dr. Don Zack of the Wilmer Glaucoma Center of Excellence has produced new
retinal ganglion cells from skin cells of adults using a method of reprogramming cells called
induced pluripotency. The new cells look and act just as ganglion cells do.
(Figure 9).
Thousands of new cells can be made in this way
and the beauty is that they are your cells, so there shouldn’t be a
problem with their being rejected. That’s when someone else’s tissue is put into you
and is attacked and killed since it’s foreign.

Figure 9: Progenitor Nerve Cells. New cells that have many characteristics of retinal ganglion cells were produced by
Glaucoma Center of Excellence researcher Don Zack and colleagues from adult cells called induced
pluripotent cells. These may someday become
the replacement cells that could restore vision lost from
glaucoma.

New cells have been
convinced to move into the retina of animal eyes and have lived there for
brief periods. No one has yet succeeded in finding a way to take the next
steps: getting the synapse connections wired up to the existing cells in
the retina and growing a fiber up to the brain. We have plans that
hopefully will beat those problems. But, more work is needed and no
therapy will be available for a number of years

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